Nivolumab Plus Ipilimumab Superior to Sunitinib as First-Line Therapy in Advanced Renal Cell Carcinoma

Nivolumab plus ipilimumab demonstrated durable clinical benefit over sunitinib for the first-line treatment of patients with advanced renal cell carcinoma (RCC) after 5 years of follow-up, according to findings from the CheckMate 214 trial.

The trial enrolled 1096 untreated patients with advanced RCC. Patients were randomized to nivolumab plus ipilimumab every 3 weeks for 4 cycles, then either nivolumab monotherapy or sunitinib daily for four 6-week cycles. The median follow-up was 67.7 months.

Researchers evaluated conditional survival outcomes (the probability of remaining alive, progression free, or in response) for participants with a minimum of 5 years follow-up, with a database lock of February 24, 2021.

In the intent-to-treat population consisting of 550 patients treated with nivolumab plus ipilimumab and 546 patients treated with sunitinib, the median overall survival (OS) was 55.7 vs 38.4 months, respectively (hazard ratio [HR], 0.72). Median progression-free survival (PFS) was 12.3 months vs 12.3 months, respectively HR, 0.86). The objective response rate was 39.3% with nivolumab plus ipilimumab vs 32.4% with sunitinib.

Point estimates for 2-year conditional OS beyond the 3-year landmark were higher with nivolumab plus ipilimumab vs sunitinib (intent-to-treat patients, 81% vs 72%; intermediate-risk/poor-risk patients, 79% vs 72%; favorable-risk patients, 85% vs 72%). Conditional PFS and response point estimates were also higher beyond 3 years with nivolumab plus ipilimumab.

For each subsequent year of survival, point estimates for conditional OS were higher or remained steady with nivolumab plus ipilimumab in patients stratified by tumor programmed death ligand 1 expression, incidence of grade ≥3 immune-mediated adverse events, body mass index, and age.

At 5 years, rates of discontinuation were high: only 6% of those treated with nivolumab and ipilimumab and 2% of patients in the sunitinib arm continued therapy.

Treatment-related adverse events (AEs) of grades 3 and 4 were lower in the nivolumab plus ipilimumab arm, at 48% vs 64% in the sunitinib arm. However, treatment-related AEs leading to discontinuation were higher in the nivolumab plus ipilimumab arm (23% vs 13%).

Source:

Motzer R, McDermott D, Escudier B, et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. Published online April 5, 2022. doi:10.1002/cncr.34180.